Vlieghe Kobe, Boudolf Véronique, Beemster Gerrit T S, Maes Sara, Magyar Zoltan, Atanassova Ana, de Almeida Engler Janice, De Groodt Ruth, Inzé Dirk, De Veylder Lieven
Department of Plant Systems Biology, Flanders Interuniversity Institute for Biotechnology, Ghent University, Technologiepark 927, Gent B-9052, Belgium.
Curr Biol. 2005 Jan 11;15(1):59-63. doi: 10.1016/j.cub.2004.12.038.
Endoreduplication or DNA replication without mitosis is widespread in nature. Well-known examples are fruit fly polytene chromosomes and cereal endosperm. Although endocycles are thought to be driven by the same regulators as those that control the G1-S transition of the mitotic cell cycle, the molecular mechanisms that differentiate mitotically dividing cells from endoreduplicating ones are largely unknown. A novel class of atypical E2F-like proteins has recently been identified and is designated E2F7 in mammals and DP-E2F-like (DEL) in Arabidopsis thaliana . We demonstrate that loss of DEL1 function resulted in increased ploidy levels, whereas ectopic expression of DEL1 reduced endoreduplication. Ploidy changes were correlated with altered expression of a subset of E2F target genes encoding proteins necessary for DNA replication. Because DEL1 proteins were postulated to antagonize the E2F pathway, we generated DEL1-E2Fa-DPa triple transgenics. DEL1 inhibited the endoreduplication phenotype, but not the ectopic cell divisions that resulted from the overexpression of both E2Fa and DPa, illustrating that DEL1 specifically represses the endocycle. Because DEL1 transcripts were detected exclusively in mitotically dividing cells, we conclude that DEL1 is an important novel inhibitor of the endocycle and preserves the mitotic state of proliferating cells by suppressing transcription of genes that are required for cells to enter the DNA endoreduplication cycle.
核内复制，即无有丝分裂的DNA复制，在自然界中广泛存在。著名的例子有果蝇的多线染色体和谷物胚乳。尽管人们认为内复制周期与控制有丝分裂细胞周期G1-S转换的调控因子相同，但区分有丝分裂细胞和核内复制细胞的分子机制在很大程度上尚不清楚。最近发现了一类新型的非典型E2F样蛋白，在哺乳动物中被命名为E2F7，在拟南芥中被命名为DP-E2F样蛋白（DEL）。我们证明，DEL1功能的丧失导致倍性水平增加，而DEL1的异位表达减少了核内复制。倍性变化与编码DNA复制所需蛋白质的E2F靶基因子集的表达改变相关。由于DEL1蛋白被认为拮抗E2F途径，我们构建了DEL1-E2Fa-DPa三转基因。DEL1抑制了核内复制表型，但不抑制由E2Fa和DPa过表达导致的异位细胞分裂，这表明DEL1特异性抑制内复制周期。因为DEL1转录本仅在有丝分裂细胞中检测到，我们得出结论，DEL1是内复制周期的一种重要新型抑制剂，通过抑制细胞进入DNA核内复制周期所需基因的转录来维持增殖细胞的有丝分裂状态。
